Apolipoprotein B mRNA editing is modulated by thyroid hormone analogs but not growth hormone administration in the rat.
Recent work has demonstrated that the unique post-transcriptional editing reaction which modifies mammalian apolipoprotein (apo) B100 mRNA, producing an in-frame stop codon in the modified (apo B48) transcript, is modulated in vivo in the rat liver by thyroid hormone (T3). We now report the results of studies undertaken to examine the effects of two synthetic T3 analogs and GH on apo B gene expression together with their effects on hepatic apo A-I, A-IV, C-III, and malic enzyme (ME)mRNAs. The T3 analogs were previously shown to exhibit similar binding to the hepatic nuclear T3 receptor (50% and 38% of native T3) but differing biopotency (18 and less than 3% of native T3). Apo B100 mRNA editing, determined by differential hybridization of polymerase chain reaction amplified apo B cDNA, demonstrated 50-56% unmodified (apo B100) mRNA in control and hypothyroid animals and this proportion was unaltered by GH (61% B100 mRNA), despite a reduction in apo B100 synthesis. Both T3 analogs altered apo B mRNA editing (12-16% B100 mRNA) and no apo B100 synthesis was detectable in vivo. Additionally, both T3 analogs produced a 4- to 10-fold induction in hepatic apo A-I and A-IV mRNA abundance, similar to the effects of native T3. GH produced no alteration in apo A-I or A-IV mRNA abundance and neither T3 analog, GH, or native T3 produced a change in apo C III mRNA abundance.(ABSTRACT TRUNCATED AT 250 WORDS)
Davidson
N O
NO
Department of Medicine, University of Chicago, Illinois 60637.
Carlos
R C
RC
Lukaszewicz
A M
AM
D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics*; D001483:Base Sequence; D015342:DNA Probes; D005786:Gene Expression Regulation / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000031:analogs & derivatives* / Q000494:pharmacology
D001055:Apolipoproteins B; D015342:DNA Probes; D012333:RNA, Messenger; D014284:Triiodothyronine; D013006:Growth Hormone